July 2019 Flavanols ERP - Review Book

Expert Review Panel for Flavanols Methods Friday, July 12, 2019 at 11:00 a.m. E.T. https://global.gotomeeting.com/join/704476749 United States (Toll Free): 1 866 899 4679, Access Code: 704-476-749#

( International Numbers )

I.

Welcome & Roll Call a. Confirmation of Quorum

II. Modification : AOAC 2012.24 a. Primary Review: Kelly Reins b. Secondary Review: Darryl Sullivan III. Discussion on Submitted Feedback IV. Next Steps/Follow Up Actions V. Adjourn

AOAC FLAVANOLS EXPERT REVIEW PANEL

METHODS AND SMPR ACCESS

• AOAC SMPR 2012.001 • METHOD ACCESS (ERP ONLY – PASSWORD REQUIRED)

AOAC OMA MODIFICATION ERP REVIEW FORM

Submission Date

2019-07-03 08:17:53

First and Last Name:

Darryl Sullivan

Organization:

Eurofins Scientific

E-mail address:

darrylsullivan@eurofinsus.com

Method Under Consideration

2012.24

To your knowledge, is this method recognized or adopted by another agency outside of AOAC? Do you support the proposed modification being submitted to AOAC? Please indicate explanations. Do you have any additional suggestions regarding the modification of this method? Please upload any supporting documentation in support or not in support of the proposed modification.

No

Yes - I support approval of these modifications with some caution.

No

Review of method modifications for AOAC Method 2012.24.doc

Review of method modifications for AOAC Method 2012.24 “ Flavanol and Procyanidin (by Degree of Polymerization 1-10) of Chocolate, Cocoa Liquors, Powder(s), and Cocoa Flavanol Extracts” By Darryl Sullivan The method authors submitted a request for method modifications including: • Modification of the analytical separation column and the gradient conditions used in the HPLC system • Replacement of the epicatechin standard with a cocoa extract calibrant that consists of DP1-7 species at known concentrations. These recommended changes were well documented and a revised manuscript was submitted. The rational for the change in HPLC column and the resulting changed in the gradient program were thoroughly explained. The substitution of the new calibration standard was well documented and I expect will actually improve the method. The single laboratory validation (SLV) that was submitted was well done and did a nice job of evaluating the method modifications. I only have one concern: the precision that was found in the SLV study shows the repeatability precision and intermediate precision having RSD’s of 1% and better. This is highly unusual for a complicated HPLC method and usually indicates that the analysts were highly trained and practiced in this procedure, before the completed the SLV. This is only something to take note of for now. I vote to approve these method modifications.

Darryl Sullivan Chief Science Officer Eurofins Scientific

Method Feedback for First Action AOAC method being considered for Final Action: In the use of AOAC Official Method 2012.24 Flavanol and Procyanidin ( by Degree of Polymerization 1-10) of Chocolate, Cocoa Liquor, Powder(s) and Cocoa Flavanol Extracts, a contract lab that did testing for our company used two different analytical columns for HPLC separation of PAC 1-10. They applied the same response factors to the peaks as outlined in the method to both separations without any adjustment. Column indicated in the published method is Develosil diol 100 Å 5 μm particle size, 250 × 4.6 mm id (Phenomenex, Torrance, CA; Cat. No. DI11546250W). Method indicates that column specified be used or its equivalent. The other column used by the lab was Luna HILIC 200 Å 5 μm particle size, 250 × 4.6 mm id (Phenomenex, Torrance, CA; Cat. No. 00G-4450-E0). Both the lab that did the testing for us and I agree that in some cases there is a significant bias between the quantitation of the higher polymer components, especially pentamer through decamer that doubles the total procyanidins reported if the Luna HILIC column is used as outlined in the method. There needs to be more specific requirements provided for defining equivalence of the column. Diana Kavolis, Staff Scientist, The Hershey Company - 717-534-6369. Dkavolis@hersheys.com

AOAC 2012.24 ERP – Flavanols ‐ Data Sharing Develosil vs. Luna Column

Samples  from The Hershey Company Tested by Eurofins US January 2019 

Luna vs Develosil Analytical Column  Total PACS mg/g Whole Product Basis

18.00

16.00

14.00

12.00

10.00

8.00

6.00

4.00

2.00

0.00

Luna Develosil

Luna vs Develosil Data

10 12 14 16 18

0 2 4 6 8

0.00 2.00 4.00 6.00 8.00 10.00 12.00 14.00 16.00 18.00

SRM 2384 ‐ Baking Chocolate

Develosil Column Column1 Column2 Column3 Column4 Column5 Column6 Column7 Column8 Column9 Column10 Column11 Control Sample number DP1 (mg/g) DP2 (mg/g) DP3 (mg/g) DP4 (mg/g) DP5 (mg/g) DP6 (mg/g) DP7 (mg/g) DP8 (mg/g) DP9 (mg/g) DP10 (mg/g) Total Flavanols and Procyanidins (mg/g) 7972552 3.02 4.61 2.48 1.86 1.15 0.826 0.527 0.369 0.27 0.156 15.3 7982651 2.94 4.36 2.51 2.01 1.31 0.951 0.669 0.507 0.359 0.183 15.8 7996234 3.67 5.35 2.56 2.01 1.3 0.977 0.686 0.526 0.336 0.183 17.4 8003409 3.37 4.89 2.41 1.9 1.27 0.924 0.634 0.501 0.328 0.181 16.4 8009765 3.79 5.49 2.65 2.09 1.34 0.986 0.662 0.498 0.343 0.184 18 8031734 3.26 4.92 2.42 1.92 1.26 0.919 0.612 0.455 0.338 0.183 16.3 Avg 3.5 5.0 2.7 2.0 1.2 0.8 0.5 0.3 0.1 0.1 16.2 1 STD 0.34 0.43 0.09 0.09 0.07 0.06 0.06 0.06 0.03 0.01 1.00 Luna Column Control Sample number DP1 (mg/g) DP2 (mg/g) DP3 (mg/g) DP4 (mg/g) DP5 (mg/g) DP6 (mg/g) DP7 (mg/g) DP8 (mg/g) DP9 (mg/g) DP10 (mg/g) Total Flavanols and Procyanidins (mg/g) 7809640 3.29 4.51 2.24 1.85 1.27 0.974 0.801 0.695 0.672 0.538 16.8 7818974 3.33 4.64 2.38 2.07 1.43 1.16 1.00 0.919 0.935 0.825 18.7 7831959 3.16 4.32 2.16 1.88 1.22 1.01 0.917 0.776 0.798 0.670 16.9 7854847 3.49 4.83 2.52 2.38 1.70 1.58 1.45 1.52 1.67 1.48 22.6 7859802 3.34 4.34 2.00 1.39 0.897 0.702 0.569 0.492 0.454 0.359 14.5 7864437 3.67 4.55 1.99 1.71 1.10 0.893 0.722 0.623 0.605 0.517 16.4 7886608 3.50 4.49 2.12 1.63 1.11 0.989 0.843 0.838 0.842 0.706 17.1 Avg 3.40 4.53 2.20 1.84 1.25 1.04 0.90 0.84 0.85 0.73 17.57 1 STD 0.17 0.18 0.20 0.32 0.26 0.27 0.28 0.33 0.39 0.36 2.54

AOAC INTERNATIONAL (updated 2011-0 5 - 11 by APOFAMS Task Force)

ALTERNATIVE PATHWAY to OFFICIAL FIRST ACTION METHOD STATUS REQUIREMENTS

Expert Review Panels

-Must be supported by relevant stakeholders.

-Constituted solely for the ERP purpose, not for Standard Method Performance Requirements (SMPR) purposes or as an extension of an SMPR.

-Consist of a minimum of seven members representing balance of key stakeholders.

-ERP constituency must be approved by the Official Methods Board (OMB).

-Holds transparent public meetings only.

-Remains in force as long as method in First Action Status.

Official First Action Method Status decision

-Must be made by an ERP constituted or reinstated post 2011-03-28 for Official First Action Status Method Approval (OFASMA). -Must be made by an ERP vetted for OFASMA purposes by OMB post 2011-03-28. -Method adopted by ERP must perform adequately against the SMPR set forth by the stakeholders. -Method must be adopted by unanimous decision of ERP on first ballot, If not unanimous, negative votes must delineate scientific reasons.

-Negative voter(s) can be overridden by 2/3 of non-negative voting ERP members after due consideration

- Method becomes Official First Action on date when ERP decision is made.

-Methods to be drafted into AOAC format by a knowledgeable AOAC staff member or designee in collaboration with the ERP and method author. -Report of OFAMS decision complete with ERP report regarding decision including scientific background (references etc) to be published concurrently with method in traditional AOAC publication venues.

Method in First Action Status and Transitioning to Final Action Status

-Further data indicative of adequate method reproducibility (between laboratory) performance to be collected. Data may be collected via a collaborative study or by proficiency or other testing data of similar magnitude. -Two years maximum transition time (additional year(s) if ERP determines a relevant collaborative study or proficiency or other data collection is in progress). -Method removed from Official First Action and OMA if no evidence of method use available at the end of the transition time. -Method removed from Official First Action and OMA if no data indicative of adequate method reproducibility is forthcoming as outlined above at the end of the transition time.

-ERP to recommend Method to Official Final Action Status to the OMB.

-OMB decision on First to Final Action Status

EXPERT REVIEW PANELS --Policies and Procedures—

Introduction Expert Review Panels (ERP) are created to provide stakeholders with an expert resource to evaluate analytical solutions to identified needs and concerns. The ERP will be tasked to search for appropriate methods, issue a “Call for Methods” in the ILM and other avenues, and critically evaluate all collected methods. The ERP will then recommend appropriate methods (as submitted or modified) for adoption as Official First Action methods or for further validation. The ERP, if requested by the Committee/Topic Advisor, would be expected to assist in identifying appropriate materials to be used in the validation studies and in reviewing the protocols for such studies. Outline of ERP establishment process An Expert Review Panel is established as follows: A stakeholder or stakeholder body submits a request for the creation of an ERP to the AOAC staff. The request includes a description of the subject area, the desired outcome, and should include a list of recommended subject experts with supporting documentation (see "Qualifications of Expert Reviewers"). Included with this list of recommended subject experts could be a recommendation for an ERP Chair. The request is forwarded to the appropriate AOAC Chief Science Officer (CSO) who identifies potential members for the ERP from a recognized Pool of Experts, a Call for Experts on the AOAC website, and from the stakeholder recommendations. The candidate list and supporting documentation are forwarded to the Chair of the OMB who will assign the review to at least two OMB members. The OMB reviewers will review the candidates for expertise and perceived conflicts of interest and the OMB may then approve the members of the ERP. A Chair for the ERP is also selected. The Chair of the ERP will organize meetings of the ERP to discuss and make recommendations relative to method recommendations, the method(s) to be further validated, and the materials to be used in the validation studies. The conclusions and recommendations of the ERP will be transmitted by the ERP Chair to the OMB and stakeholder body. The stakeholder body will proceed with implementation of the ERP's recommendations by organizing the appropriate SLV study and other items needed for application. Pool of Potential Expert Reviewers : Candidates for ERPs are pulled from the following sources. Upon acceptance of the request for the formation of an ERP, a Call for Experts is posted on the AOAC website for a minimum of two weeks. Candidates can then contact AOAC with their interest and credentials. Also, AOAC maintains a Pool of Experts database containing a list of

Approved by Official Methods Board, November 13, 2008 Approved by AOAC Board of Directors, December 9, 2008 Appeals Process Appended – September 2009 Revisedby AOAC Board of Directors, May 25, 2011

Page 1 of 6

AOAC members willing to serve as experts and cataloging their education, experience, and other applicable credentials. Candidates can also be recommended by the stakeholder(s). Note: Candidates (except for the chair) do not need to be members of AOAC. The appointment of experts to an ERP will be for a minimum of 3 years. Qualification of Expert Reviewers: To qualify as an Expert Reviewer, the candidate must meet one of the following requirements: (1) Demonstrated knowledge in the appropriate scientific disciplines. (2) Demonstrated knowledge regarding data relevant to adequate method performance. (3) Demonstrated knowledge of practical application of analytical methods to bona fide diagnostic requirements. These qualifications must be clearly described in a CV submitted to the CSO and kept on file at AOAC headquarters. Duties: Members of the Pool of Experts will be called upon to serve on ERPs as needed, and to review documents prepared in the course of the project. These documents may include: (1) procedural documents on how methods will be selected and how single laboratory validation studies will be done; (2) methods submitted for consideration as Official First Action Methods; (3) methods submitted for selection for further validation studies; (4) protocols to be used for single laboratory validation studies; (5) the selection of methods to be considered for full collaborative studies; and (6) validation study reports. Expert Review Panel: The CSO selects candidates for an ERP from the Pool of Experts database, the Call for Experts on the AOAC website, and from candidates recommended by the stakeholders. Selection of ERP candidates is based upon their knowledge and experience to adequately evaluate the scope of the study and the anticipated number of submitted methods. The size of the ERP will be sufficient to assure the necessary expertise is present. The CSO may recommend one of the Panel members to serve as Chair. The CSO submits the following to the OMB Chair: The original submission package, a list of all candidates considered for inclusion on the ERP, the slate of recommended candidates, and a list of possible alternates. Explanations for the ERP choices may be included by either the CSO or a stakeholder if desired. The OMB Chair will delegate two members of the OMB to perform a review. The reviewers submit their recommendations in writing to the OMB. The OMB then votes on the reviewers’ recommendations. This vote can be either by email or during an OMB meeting. The OMB may choose not to select one or more individuals on the Panel as submitted and may or may not accept the recommendation of the CSO for the panel Chair. A majority of those voting will be required for approval. The vote of the Chair will break any tie. The CSO, ERP members, and stakeholder body are notified of the vote within one week. Conflict of Interest: It is incumbent upon each ERP member to avoid any known or potential conflicts of interest and make these known to the CSO and OMB Chair. Each pool member chosen for an ERP will be asked to agree to the AOAC Policies and Procedures on Conflicts of Interest evidenced by completing a Conflict of Interest Form.

Approved by Official Methods Board, November 13, 2008 Approved by AOAC Board of Directors, December 9, 2008 Appeals Process Appended – September 2009 Revisedby AOAC Board of Directors, May 25, 2011

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If a Pool member being considered to serve on any particular panel is an author, or his/her laboratory is the source of a method under consideration by the Panel, they must so indicate to the CSO or OMB Chair. At the discretion of the CSO or OMB, the names of such Pool members may be removed from consideration, or they may be considered to serve on the ERP with the understanding that a deliberate effort will be required to avoid any known or potential conflicts of interest. In these latter cases, assignments of individual methods for peer review will be made in such a way by the Chair that ERP members will not review any method for which they are an author or co-author, or for which their laboratory is the source; and, most importantly, the Chair will require that they abstain from voting on such a method during the final method selection process. The CSO or OMB may also allow Pool members that qualify under the requirements of expert reviewers, but for whom there is a known or potential conflict of interest to be present as an observer on any particular Panel. In these cases, and only at the discretion of the Chair, observers may provide comments, but only if and when called upon by the Chair to do so. Non-disclosure Statement: All members of an ERP must have signed the AOAC Volunteer Acceptance Form. For certain contracts, each Pool member or observer chosen may be asked to sign a non-disclosure statement agreeing not to discuss or disclose confidential information presented and discussed during meetings of the ERP. Meetings of the ERP: The ERP Chair will organize meetings of the ERP, to review the methods and accompanying validation data, score them numerically, and prepare a summary report. Meetings of the ERP can include voting members of the Panel, and non-voting members (AOAC staff, stakeholder members, and observers). The CSO may assist the Panel Chair in facilitating meetings. The members of the Panel are to review distributed documents before the meeting. To facilitate the process, the Chair may assign primary and secondary reviewers for each method. The primary and secondary reviewers prepare a short critique of the method that is distributed or presented to the ERP. If both the primary and secondary reviewers conclude that the method should not be considered further, the ERP Chair may call for a vote by the Panel; if a unanimous vote to drop a method without further discussion results, the Chair removes the method from further consideration. The Panel then discusses each of the remaining methods in turn. Method Selection Process: The ERP will evaluate all of the methods in a scientifically unbiased manner. Occasionally, a large number of analytical methods of variable quality are encountered. When this occurs, the following “pre-screening” procedure is suggested to eliminate methods that are not satisfactory. The Chair of the ERP with the assistance of at least one other member of the ERP may review all of the methods and remove unsatisfactory methods from consideration. The remainder of the methods would be sent to the ERP members for review.

Approved by Official Methods Board, November 13, 2008 Approved by AOAC Board of Directors, December 9, 2008 Appeals Process Appended – September 2009 Revisedby AOAC Board of Directors, May 25, 2011

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The basic requirements for selection of methods for further validation studies will be: fitness for purpose, applicability to the scope needed, clarity of method description, satisfactory performance characteristics, and single laboratory validation data. To assist the Panel, the AOAC will provide a “Methods Selection Worksheet,” which may be modified at the discretion of the ERP. ERP members will identify the best method(s) for further validation, and identify any modifications to be made to the method. An example of the Method Selection Worksheet is attached. Samples: The ERP will be asked to recommend the specific materials (matrices) to be included in the subsequent validation studies, along with detailed justifications. Summary Report: The Chair of the ERP prepares a Summary Report clearly enunciating the recommendations of the Panel, the manner in which these conclusions were reached, any modifications of the method(s) chosen, and the materials (matrices) to be included in the validation studies. The report is to be submitted to the ERP in a timely fashion after the concluding ERP meeting. Comments are also due back to the ERP Chair in a timely fashion. The report is then sent to the stakeholders and a copy is forwarded to the Chair of the OMB. Post-ERP Activities: AOAC retains the right to call on the panelists, as well as members of the Industry Groups, for continued assistance in the subsequent validation studies. This may include (1) help in obtaining the required samples for use in the subsequent validation studies, as well as participating laboratories; (2) help in developing and reviewing the validation study protocols; and (3) help in reviewing the data resulting from the validation studies and reviewing the manuscript describing the results. These activities will be coordinated by the CSO.

Method Selection Worksheet

Method Title: Method Number: Overall evaluation score (1being lowest, 10 being highest): Additional Factors to Consider:

Recommendation: Signature (date):

Approved by Official Methods Board, November 13, 2008 Approved by AOAC Board of Directors, December 9, 2008 Appeals Process Appended – September 2009 Revisedby AOAC Board of Directors, May 25, 2011

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Expert Review Panel Selection Criteria: 1. AOAC paid consultants and AOAC staff should not act as Chairs of ERPs. 2. Members of the BoD may act as voting members but it is recommended that they sit as non-voting members of the panel, unless the CSO can demonstrate that there are so few experts in the field available to the community that they are needed to move the project forward.

3. Paid consultants of AOAC and AOAC staff may not serve as voting members on ERPs.

4. If a single business location is represented by more than one person on an ERP, that location shall have only one vote.

5. The Chair of the ERP must be a member of AOAC INTERNATIONAL.

Appeals Process: ERP - Openness of Process and Appeals:

The entire ERP review process is fully open. Any interested party (person, agency, organization, association, company, Chief Scientific Officer (CSO), or group) shall have the right to comment. Appeals or comments are sent to the AOAC Staff. Technical decisions by the ERP are final and are not subject to review or appeal. Other questions or issues regarding procedures, conflict of interest, or impropriety may be

appealed to the President of the AOAC INTERNATIONAL. All written concerns will be considered and given a response.

If there is disagreement between the CSO and the Official Methods Board reviewers, the CSO may appeal to the Chair of the Official Methods Board for consideration. The Official Methods Board can select an impartial panel to review the issue, which must report to the Official Methods Board with a resolution within 21 days of its assignment.

Approved by Official Methods Board, November 13, 2008 Approved by AOAC Board of Directors, December 9, 2008 Appeals Process Appended – September 2009 Revisedby AOAC Board of Directors, May 25, 2011

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Appeal From CSO or any interested party

President of AOAC Int’l

Chair of the Official Methods Board

AOAC Staff

From CSO

From interested party

Minor Resolutions to CSO

Response to Appeal Determined

Assign >2 reviewers from OMB

AOAC Staff

Response to OMB within 21 days

Notify interested party

Unresolved

OMB vote (majority vote)

Resolved

Unresolved

Approved by Official Methods Board, November 13, 2008 Approved by AOAC Board of Directors, December 9, 2008 Appeals Process Appended – September 2009 Revisedby AOAC Board of Directors, May 25, 2011

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Appendix G: Procedures and Guidelines for the Use of AOAC Voluntary Consensus Standards to Evaluate Characteristics of a Method of Analysis

that are required to be resolved prior to adoption as a Final Action Official Method. Methods adopted by an ERP as First Action Official Methods may not be in AOAC Official Methods format. Method developers/ authors are asked to assist AOAC to rewrite the method and accompanying manuscript into an AOAC-acceptable format. Two-Year First Action Evaluation Period Under the new pathway, a method may be designated as a First Action Official Method based on the collective judgment of an ERP. Official Methods remain as First Action for a period of about 2 years. During the First Action period, the method will be used in laboratories, and method users will be asked to provide feedback on the performance of the method. As previously described, two (or more) ERP members are assigned to lead the review of candidate methods for adoption as First Action Official Methods .After a method has been adopted as FirstAction, these lead reviewers are expected to keep track of the use of and experience with the First Action Official Method . At the conclusion of the 2-year evaluation period, one or both of the lead reviewers will report back to the ERP on the experience of the First Action Official Method. The presiding ERP will monitor the performance of the method, and, at the completion of the 2-year First Action evaluation period, determine whether the method should be recommended to the OMB for adoption as an AOAC Final Action Official Method . It is also possible that First Action Official Methods are not recommended for Final Action. There are two possibilities for an ERP to decide not to proceed with a First Action method: ( 1 ) feedback frommethod users indicates that a First Action method is not performing as well in the field as was expected; or ( 2 ) another method with better performance characteristics has been developed and reviewed. In either case, the ERPmay choose to repeal the First Action status of a method. OMB Review The OMB will review all methods recommended for Final Action or repeal by the ERP, and will consider a number of factors in their decision.Aguidance document for factors to consider is provided on the AOAC website at http://www.aoac.org/vmeth/OMB_ERP_Guidance. pdf. Some of the factors identified by the guidance document for OMB consideration are ( 1 ) feedback from method users, ( 2 ) comparison to the appropriate SMPR, ( 3 ) results from single-laboratory validation, ( 4 ) reproducibility/uncertainty and probability of detection, ( 5 ) availability of reference materials, and ( 6 ) safety concerns. Conclusion The new pathway to Official Methods SM is deliberately designed to avoid creation of elaborate review systems. The intent of the model is for method experts to use their scientific knowledge, experience, and good judgment to identify and adopt the best methods possible for the analytical need.

Expert Review Panels, Official Methods Board, First and Final Action Official Methods SM In early 2011, an AOAC Presidential Task Force recommended that AOAC use Expert review panels (ERPs) to assess candidate methods against standard method performance requirements (SMPRs) to ensure that adopted First Action Official Methods SM are fit for purpose. Formation of an ERP AOAC ERPs are authorized to adopt candidate methods as First Action Official Methods and to recommend adoption of these methods to Final Action Official Methods status. Scientists are recruited to serve on ERPs by a variety of ways. Normally, a call for experts is published at the same time as a call for methods is posted. Interested scientists are invited to submit their curriculum vitae (CV) for consideration. Advisory panel, stakeholder panel, and working group members may make recommendations toAOAC for ERP members. All CVs are reviewed and evaluated for expertise by the AOAC Chief Scientific Officer (CSO). The CVs and CSO evaluations are forwarded to the OMB for formal review. Both the CSO and OMB strive to ensure that the composition of a proposed ERP is both qualified and represent the various stakeholder groups. The recommended ERP members are submitted to the AOAC president who then appoints the ERP members. Review of Methods Methods submitted to AOAC in response to a call for methods are collected and compiled by AOAC staff. The AOAC CSO and working group chair perform a preliminary review of the methods and classify them into three categories: ( 1 ) fully developed and written methods that appear to meet SMPRs; ( 2 ) fully developed and written methods that may or may not meet SMPRs; and ( 3 ) incomplete methods with no performance data. Method submitters are apprised of the evaluation of their methods. Method developers with submissions that are classified as Category 2 or 3 are encouraged to provide additional information if available. A list of all the submitted methods and their classifications are posted for public review. Usually, two ERP members (sometimes more) are assigned to lead the review of each Category 1 method. An ERP meeting is convened to review the methods. ERP meetings are open to all interested parties, and are usually well-attended events with about 50–60 attendees common. Each Category 1 method is reviewed and discussed by the ERP. If stakeholders have designated the method to be a dispute resolution method (as stated in the SMPR), then the ERP is asked to identify the single best candidate method to be adopted as a First Action Official Method . If the SMPR does not specify the need for a dispute resolution method, then the ERP may choose to adopt all methods that meet the SMPRs, or may choose to adopt the single best method in their collective, expert opinion. In addition, an ERPmay choose to require changes to a candidate method as part of its First Action adoption and/or identify issues

© 2014 AOAC INTERNATIONAL

V ඗ඔඝඖගඉකඡ C ඗ඖඛඍඖඛඝඛ S ගඉඖඌඉකඌඛ

AOAC O ඎඎඑඋඑඉඔ M ඍගඐ඗ඌඛ ඗ඎ A ඖඉඔඡඛඑඛ (2014)

Appendix G, p. 2

These methods are then published as First Action Official Methods, and used by analysts while additional information about the method is collected. Method reviewers may consider other forms of information in lieu of the traditional collaborative study to demonstrate method reproducibility. Additional Information Coates, S. (2012) “Alternative Pathway,” Inside Laboratory Management 16 (3), pp 10–12 Expert Review Panels, Policies and Procedures , AOAC INTERNATIONAL, http://www.aoac.org/News/EXPERT%20 REVIEW%20PANELS%20final%20revision.pdf Standard Format and Guidance for AOAC Standard Method Performance Requirement (SMPR) Documents, AOAC INTERNATIONAL, http://www.aoac.org/ISPAM/pdf/3.5%20 SMPR%20Guideline%20v12.1.pdf Guidance Documents Requirements for First Action Official Methods SM Status See Figure 1 for process flowchart. Expert Review Panels ( 1 ) Supported by relevant stakeholders. ( 2 ) Constituted solely for the ERP purpose, not for SMPR purposes or as an extension of an SMPR. ( 3 ) Consist of a minimum of seven members representing a balance of key stakeholders. A quorum is the presence of seven members or 2/3 of total vetted ERP membership, whichever is greater. ( 4 ) ERP constituency must be approved by the OMB. ( 5 ) Hold transparent public meetings only. ( 6 ) Remain in force as long as method in First Action status. First Action Official Method SM Status Decision ( 1 ) Must be made by an ERP constituted or reinstated post March 28, 2011 for First Action Official Method SM status approval. ( 2 ) Must be made by an ERP vetted for First Action Official Method SM status purposes by OMB post March 28, 2011. ( 3 ) Method adopted by ERP must perform adequately against the SMPR set forth by the stakeholders. ( 4 ) Method must be adopted by unanimous decision of ERP on first ballot. If not unanimous, negative votes must delineate scientific reasons. ( 5 ) Negative voter(s) can be overridden by 2/3 of voting ERP members after due consideration. ( 6 ) Method becomes Official First Action on date when ERP decision is made. ( 7 ) Methods to be drafted intoAOAC format by a knowledgeable AOAC staff member or designee in collaboration with the ERP and method author. ( 8 ) Report of First Action Official Method SM status decision complete with ERP report regarding decision, including scientific background (references, etc.), to be published concurrently with method in traditional AOAC publication venues.

Funded Stakeholder Panel

x x x

Managed by AOAC HQ Properly vetted by OMB

Carefully documented and transparent

Working Groups

Standard Method

x Managed by AOAC HQ x Carefully documented and transparent

Performance Requirements

Expert Review Panels

Call for Methods & Literature Search

x Managed by AOAC HQ x Properly vetted by OMB x Carefully documented and transparent

Official First Action Method

JAOAC OMA Web ILM

x ERPs continue to monitor for two years, until method is either advanced or removed from system (period is extendable for active data collection) x ERP recommends Final Action to OMB x OMB grants Final Action status

Figure 1. Summary of standards development through Official Methods of Analysis .

Method in First Action Status and Transitioning to Final Action Status ( 1 ) Further data indicative of adequate method reproducibility (between laboratory) performance to be collected. Data may be collected via a collaborative study or by proficiency or other testing data of similar magnitude. ( 2 ) Two years maximum transition time [additional year(s) if ERP determines a relevant collaborative study or proficiency or other data collection is in progress]. ( 3 ) Method removed from Official First Action and OMA if no evidence of method use available at the end of the transition time. ( 4 ) Method removed from Official First Action and OMA if no data indicative of adequate method reproducibility is forthcoming as outlined above at the end of the transition time. ( 5 ) ERP to recommend method to Final Action Official status to the OMB. ( 6 ) OMB decision on First to Final Action status. These guidance documents were approved by the AOAC Board of Directors on May 25, 2011. Revised in February 2014 to include the definition of a quorum under the section Expert Review Panels , item ( 3 ).

© 2014 AOAC INTERNATIONAL

AOAC O ඎඎඑඋඑඉඔ M ඍගඐ඗ඌඛ ඗ඎ A ඖඉඔඡඛඑඛ (2014)

V ඗ඔඝඖගඉකඡ C ඗ඖඛඍඖඛඝඛ S ගඉඖඌඉකඌඛ Appendix G, p. 3

( b ) Guidance and support can be obtained from the AOAC Technical Division on Reference Materials. D. Single-Laboratory Validation ( a ) Data demonstrating response linearity, accuracy, repeatability, LOD/LOQ, and matrix scope must be present. Experimental designs to collect this data may vary with the method protocol and the intended use of the method. ( b ) Resources can be identified by the AOAC Statistics Committee. E. Reproducibility/Uncertainty and Probability of Detection ( a ) For quantitative methods, data demonstrating reproducibility and uncertainty must be present. Experimental designs to collect this data may vary with the method protocol, available laboratories, and the intended use of the method (i.e., collaborative studies, proficiency testing, etc.). ( b ) For qualitative methods, data must be present demonstrating the probability of detection at specified concentration levels as defined by the SMPR. Experimental designs to collect this data may vary with the method protocol, available laboratories, and the intended use of the method. ( c ) Guidance and support can be obtained from the AOAC Statistics Committee. F. Comparison to SMPR ( a ) Document method performance versus SMPR criteria. Note which SMPR criteria are met. For SMPR criteria not met, the ERP documents the reasoning why the method is still acceptable. ( b ) Data is present to assure the matrix and analyte scopes are covered. This is critical for methods used for dispute resolutions. G. Feedback from Users of Method ( a ) Document positive and negative feedback from users of the method during the trial period. ( b ) Feedback from users demonstrating method ruggedness should be documented. ( c ) Assess the future availability of vital equipment, reference materials, and supplies. H. ERP Recommendations to Repeal First Action Methods Recommendations to repeal First Action methods shall be accompanied with detailed reasons for the decision. The First to Final Action guidance for ERPs was approved by the OMB in December 2011 and effective as of February 1, 2012.

First Action to Final Action Methods: Guidance for AOAC Expert Review Panels

In December 2011, the Official Methods Board (OMB) approved a guidance document for ERPs to support their work as they deliberate on methods, adopt methods as Official First Action, and, subsequently, track method usage and performance between First Action status and Final Action consideration. The guideline is based on parameters of a method that the OMB will consider when deliberating on methods recommended for Final Action status. ERPs are to use this guideline in their deliberations. ERPs working within the AOAC process may recommend a First Action status method be elevated to Final Action status. Such a recommendation leverages the ERP’s high level of expertise supported by data from the initial evaluation, and results from the subsequent 2-year method performance evaluation period. The OMB receives the recommendation with supporting documentation, and determines if Final Action status is warranted. OMB’s review verifies the method process was conducted in compliance with the guidelines and protocols of the Association. For transparency and to expedite the review process, the main areas OMB will review when evaluating ERP recommendations to promote methods to Final Action are listed below. Documentation of the areas listed below will also increase confidence in method performance and assist users to properly and safely perform the ( a ) A method’s applicability to the identified stakeholder needs is best assessed by the stakeholder panel and should be a part of the process from the onset. OMB liaisons will remind stakeholder panels to maintain this focus point. ( b ) OMB may ask ERPs and stakeholder panels for feedback to improve the applicability of the method, such as potential method scope expansions and potential points of concern. B. Safety Concerns ( a ) A safety review must be performed for a method to be recognized as First Action. ( b ) All safety concerns identified during the 2-year evaluation period must be addressed. ( c ) Guidance and support can be obtained from the AOAC Safety Committee. C. Reference Materials ( a ) Document efforts undertaken to locate reference materials. Methods may still progress to Final Action even if reference materials are not available. methods at their locations. A. Method Applicability

© 2014 AOAC INTERNATIONAL

Appendix W

POLICY AND PROCEDURES ON VOLUNTEER CONFLICT OF INTEREST

Statement of Policy

While it is not the intention of AOAC INTERNATIONAL (AOAC) to restrict the personal, professional, or proprietary activities of AOAC members nor to preclude or restrict participation in Association affairs solely by reason of such activities, it is the sense of AOAC that conflicts of interest or even the appearance of conflicts of interest on the part of AOAC volunteers should be avoided. Where this is not possible or practical under the circumstances, there shall be written disclosure by the volunteers of actual or potential conflicts of interest in order to ensure the credibility and integrity of AOAC. Such written disclosure shall be made to any individual or group within the Association which is reviewing a recommendation which the volunteer had a part in formulating and in which the volunteer has a material interest causing an actual or potential conflict of interest. AOAC requires disclosure of actual or potential conflicts of interest as a condition of active participation in the business of the Association. The burden of disclosure of conflicts of interest or the appearance of conflicts of interest falls upon the volunteer. A disclosed conflict of interest will not in itself bar an AOAC member from participation in Association activities, but a three-fourths majority of the AOAC group reviewing the issue presenting the conflict must concur by secret ballot that the volunteer's continued participation is necessary and will not unreasonably jeopardize the integrity of the decision-making process. Employees of AOAC are governed by the provision of the AOAC policy on conflict of interest by staff. If that policy is in disagreement with or mute on matters covered by this policy, the provisions of this policy shall prevail and apply to staff as well. 1. A volunteer who is serving as a committee member or referee engaged in the evaluation of a method or device; who is also an employee of or receiving a fee from the firm which is manufacturing or distributing the method or device or is an employee of or receiving a fee from a competing firm. 2. A volunteer who is requested to evaluate a proposed method or a related collaborative study in which data are presented that appear detrimental (or favorable) to a product distributed or a position supported by the volunteer's employer. 3. A referee who is conducting a study and evaluating the results of an instrument, a kit, or a piece of equipment which will be provided gratis by the manufacturer or distributor to one or more of the participating laboratories, including his or her own laboratory, at the conclusion of the study. 4. Sponsorship of a collaborative study by an interest (which may include the referee) which stands to profit from the results; such sponsorship usually involving the privilege granted by the investigator to permit the sponsor to review and comment upon the results prior to AOAC evaluation. Illustrations of Conflicts of Interest

5. A volunteer asked to review a manuscript submitted for publication when the manuscript contains information which is critical of a proprietary or other interest of the reviewer.

The foregoing are intended as illustrative and should not be interpreted to be all-inclusive examples of conflicts of interest AOAC volunteers may find themselves involved in.

Do's and Don't's

Do avoid the appearance as well as the fact of a conflict of interest.

Do make written disclosure of any material interest which may constitute a conflict of interest or the appearance of a conflict of interest.

Do not accept payment or gifts for services rendered as a volunteer of the Association without disclosing such payment or gifts.

Do not vote on any issue before an AOAC decision-making body where you have the appearance of or an actual conflict of interest regarding the recommendation or decision before that body.

Do not participate in an AOAC decision-making body without written disclosure of actual or potential conflicts of interest in the issues before that body.

Do not accept a position of responsibility as an AOAC volunteer, without disclosure, where the discharge of the accepted responsibility will be or may appear to be influenced by proprietary or other conflicting interests.

Procedures

Each volunteer elected or appointed to an AOAC position of responsibility shall be sent, at the time of election or appointment, a copy of this policy and shall be advised of the requirement to adhere to the provisions herein as a condition for active participation in the business of the Association. Each volunteer, at the time of his or her election or appointment, shall indicate, in writing, on a form provided for this purpose by AOAC, that he or she has read and accepts this policy. Each year, at the spring meeting of the AOAC Board of Directors, the Executive Director shall submit a report certifying the requirements of this policy have been met; including the names and positions of any elected or appointed volunteers who have not at that time indicated in writing that they have accepted the policy. Anyone with knowledge of specific instances in which the provisions of this policy have not been complied with shall report these instances to the Board of Directors, via the Office of the Executive Director, as soon as discovered.

* * * * * *

Adopted: March 2, 1989 Revised: March 28, 1990 Revised: October 1996 Reviewed by outside counsel March 2000 (Fran Dwornik) and found to be current and relevant

Appendix U

ANTITRUST POLICY STATEMENT AND GUIDELINES

Introduction

It is the policy of AOAC INTERNATIONAL (AOAC) and its members to comply strictly with all laws applicable to AOAC activities. Because AOAC activities frequently involve cooperative undertakings and meetings where competitors may be present, it is important to emphasize the on-going commitment of our members and the Association to full compliance with national and other antitrust laws. This statement is a reminder of that commitment and should be used as a general guide for AOAC and related individual activities and meetings.

Responsibility for Antitrust Compliance

The Association's structure is fashioned and its programs are carried out in conformance with antitrust standards. However, an equal responsibility for antitrust compliance -- which includes avoidance of even an appearance of improper activity -- belongs to the individual. Even the appearance of improper activity must be avoided because the courts have taken the position that actual proof of misconduct is not required under the law. All that is required is whether misconduct can be inferred from the individual's activities. Employers and AOAC depend on individual good judgment to avoid all discussions and activities which may involve improper subject matter and improper procedures. AOAC staff members work conscientiously to avoid subject matter or discussion which may have unintended implications, and counsel for the Association can provide guidance with regard to these matters. It is important for the individual to realize, however, that the competitive significance of a particular conduct or communication probably is evident only to the individual who is directly involved in such matters. In general, the U.S. antitrust laws seek to preserve a free, competitive economy and trade in the United States and in commerce with foreign countries. Laws in other countries have similar objectives. Competitors (including individuals) may not restrain competition among themselves with reference to the price, quality, or distribution of their products, and they may not act in concert to restrict the competitive capabilities or opportunities of competitors, suppliers, or customers. Although the Justice Department and Federal Trade Commission generally enforce the U.S. antitrust laws, private parties can bring their own lawsuits. Penalties for violating the U.S. and other antitrust laws are severe: corporations are subject to heavy fines and injunctive decrees, and may have to pay substantial damage judgments to injured competitors, suppliers, or customers. Individuals are subject to criminal prosecution, and will be punished by fines and imprisonment. Under current U.S. federal sentencing guidelines, individuals found guilty of bid rigging, price fixing, or market allocation must be sent to jail for at least 4 to 10 months and must pay substantial minimum fines. Antitrust Guidelines

Since the individual has an important responsibility in ensuring antitrust compliance in AOAC activities, everyone should read and heed the following guidelines.

1. Don't make any effort to bring about or prevent the standardization of any method or product for the purpose or intent of preventing the manufacture or sale of any method or product not conforming to a specified standard 2. Don't discuss with competitors your own or the competitors' prices, or anything that might

affect prices such as costs, discounts, terms of sale, distribution, volume of production, profit margins, territories, or customers.

3. Don't make announcements or statements at AOAC functions, outside leased exhibit space, about your own prices or those of competitors.

4. Don't disclose to others at meetings or otherwise any competitively sensitive information.

5. Don't attempt to use the Association to restrict the economic activities of any firm or any individual.

6. Don't stay at a meeting where any such price or anti-competitive talk occurs.

7. Do conduct all AOAC business meetings in accordance with AOAC rules. These rules require that an AOAC staff member be present or available, the meeting be conducted by a knowledgeable chair, the agenda be followed, and minutes be kept.

8. Do confer with counsel before raising any topic or making any statement with competitive ramifications.

9. Do send copies of meeting minutes and all AOAC-related correspondence to the staff member involved in the activity.

10. Do alert the AOAC staff to any inaccuracies in proposed or existing methods and statements issued, or to be issued, by AOAC and to any conduct not in conformance with these guidelines.

Conclusion

Compliance with these guidelines involves not only avoidance of antitrust violations, but avoidance of any behavior which might be so construed. Bear in mind, however, that the above antitrust laws are stated in general terms, and that this statement is not a summary of applicable laws. It is intended only to highlight and emphasize the principal antitrust standards which are relevant to AOAC programs. You must, therefore, seek the guidance of either AOAC counsel or your own counsel if antitrust questions arise.

Adopted by the AOAC Board of Directors: September 24, 1989 Revised: March 11, 1991 Revised October 1996

Appendix V

POLICY ON THE USE OF THE ASSOCIATION NAME, INITIALS, IDENTIFYING INSIGNIA, LETTERHEAD, AND BUSINESS CARDS

Introduction

The following policy and guidelines for the use of the name, initials, and other identifying insignia of AOAC INTERNATIONAL have been developed in order to protect the reputation, image, legal integrity and property of the Association. The name of the Association, as stated in its bylaws, is "AOAC INTERNATIONAL". The Association is also known by its initials, AOAC, and by its logo, illustrated below, which incorporates the Association name and a representation of a microscope, book, and flask. The AOAC logo is owned by the Association and is registered with the U.S. Patent and Trademark Office.

6JG HWNN #UUQEKCVKQP KPUKIPKC KNNWUVTCVGF DGNQY KU EQORTKUGF QH VJG NQIQ CPF VJG VCINKPG 6JG 5EKGPVKHKE #UUQEKCVKQP &GFKECVGF VQ #PCN[VKECN 'ZEGNNGPEG UJQYP DGNQY 6JG V[RGHCEG WUGF KU .CTIQ 6JG #1#% VCINKPG KU QYPGF D[ VJG #UUQEKCVKQP CPF KU TGIKUVGTGF YKVJ VJG 7 5 2CVGPV CPF 6TCFGOCTM QHHKEG

Policy

Policy on the use of the Association's name and logo is established by the AOAC Board of Directors as follows:

“The Board approves and encourages reference to the Association by name, either as AOAC INTERNATIONAL or as AOAC; or reference to our registered trademark, AOAC®, in appropriate settings to describe our programs, products, etc., in scientific literature and other instances so long as the reference is fair, accurate, complete and truthful and does not indicate or imply unauthorized endorsement of any kind. The insignia (logo) of AOAC INTERNATIONAL is a registered trade and service mark and shall not be reproduced or used by any person or organization other than the Association, its elected and appointed officers, sections, or committees, without the prior written permission of the Association. Those authorized to use the AOAC INTERNATIONAL insignia shall use it only for